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POLE2 Regulates Apoptosis of Oral Squamous Cell Carcinoma Cells through the PI3K/AKT Signaling Pathway

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Abstract

Objective

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, but its occurrence and progression mechanisms remain unclear. In addition-there is a lack of effective targeting drugs. The second major subunit of DNA polymerase (POLE2) catalyzes the prolongation of new strand replication and modifies exonuclease domain activity. Our previous study found that POLE2 was associated with OSCC progression, but the mechanism remains unclear.

Methods

The expression of POLE2 in OSCC tissues was detected using immunological assays. Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC. POLE2 expression was inhibited in OSCC cells, and the effects of gene and protein expression were detected using RT-PCR and Western blotting. The POLE2 knockout model was constructed by transfecting a lentiviral vector. Cell proliferation, apoptosis, and migration were detected using various assays including colony formation, MTT, flow cytometry, wound healing assay, Transwell assay, and the Human Apoptosis Antibody Array. The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice. After 30 days, tumors were removed under anesthesia and tumor weight and dimension were recorded. Tumor cell proliferation was analyzed using Ki67 staining.

Results

POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues. In addition, POLE2 gene levels were statistically correlated with tumor classification and prognosis. Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro. Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation. We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3, CD40, CD40L, DR6, Fas, IGFBP-6, p21, and SMAC. In addition, POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway.

Conclusion

POLE2 is closely related to the progression of OSCC. Thus, POLE2 may be a potential target for OSCC treatment.

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Acknowledgements

We would like to thank the Department of Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology for the data support of this retrospective study.

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Author notes

  1. The authors contributed equally to this work.

Authors and Affiliations

  1. Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Ming-yu Sun & Zheng-yu Shen

  2. School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Ming-yu Sun & Zheng-yu Shen

  3. Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China

    Ming-yu Sun & Zheng-yu Shen

  4. Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266000, China

    Lin Wang

  5. Key Laboratory of Oral Clinical Medicine, Qingdao, 266000, China

    Lin Wang

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  1. Ming-yu Sun
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  2. Lin Wang
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Corresponding author

Correspondence to Zheng-yu Shen.

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All authors declare that they have no direct conflicts of interest.

Additional information

This study was supported by grants from the National Natural Science Foundation of China (No. 82203418) and the Natural Science Foundation of Hubei Province (No. 2022CFB286 and No. 2021CFB589).

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Sun, My., Wang, L. & Shen, Zy. POLE2 Regulates Apoptosis of Oral Squamous Cell Carcinoma Cells through the PI3K/AKT Signaling Pathway. CURR MED SCI 43, 1162–1172 (2023). https://doi.org/10.1007/s11596-023-2813-7

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  • DOI: https://doi.org/10.1007/s11596-023-2813-7

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